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J Exp Med. 2018 Jun 4;215(6):1627-1647. doi: 10.1084/jem.20180247. Epub 2018 Apr 11.

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.

Cronk JC1,2,3,4, Filiano AJ1,2, Louveau A1,2, Marin I1,2,3, Marsh R1,2, Ji E1,2, Goldman DH1,2,3, Smirnov I1,2, Geraci N1, Acton S5, Overall CC6,2, Kipnis J7,2,3,4.

Author information

1
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA.
2
Department of Neuroscience, University of Virginia, Charlottesville, VA.
3
Graduate Program in Neuroscience, University of Virginia, Charlottesville, VA.
4
Medical Scientist Training Program, University of Virginia, Charlottesville, VA.
5
Virginia Image and Video Analysis Laboratory, Department of Electrical and Computer Engineering and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA.
6
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA chris.overall@virginia.edu.
7
Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA kipnis@virginia.edu.

Abstract

Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.

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